|
1
|
Kumar M, Gupta S, Kalia K, Kumar D. Role of Phytoconstituents in Cancer Treatment: A Review. RECENT ADVANCES IN FOOD, NUTRITION & AGRICULTURE 2024; 15:115-137. [PMID: 38369892 DOI: 10.2174/012772574x274566231220051254] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/04/2023] [Revised: 11/03/2023] [Accepted: 11/07/2023] [Indexed: 02/20/2024]
Abstract
Over the years, natural compounds have become a significant advancement in cancer treatment, primarily due to their effectiveness, safety, bio-functionality, and wide range of molecular structures. They are now increasingly preferred in drug discovery due to these attributes. These compounds, whether occurring naturally or with synthetic modifications, find applications in various fields like biology, medicine, and engineering. While chemotherapy has been a successful method for treating cancer, it comes with systemic toxicity. To address this issue, researchers and medical practitioners are exploring the concept of combinational chemotherapy. This approach aims to reduce toxicity by using a mix of natural substances and their derivatives in clinical trials and prescription medications. Among the most extensively studied natural anticancer compounds are quercetin, curcumin, vincristine, and vinblastine. These compounds play crucial roles as immunotherapeutics and chemosensitizers, both as standalone treatments and in combination therapies with specific mechanisms. This review article provides a concise overview of the functions, potentials, and combinations of natural anticancer compounds in cancer treatment, along with their mechanisms of action and clinical applications.
Collapse
Affiliation(s)
- Manish Kumar
- Department of Pharmacy, IEC College of Eng & Tech. Gautam Buddha Nagar, India
| | | | | | - Dharmendra Kumar
- Department of Pharmacy, IEC College of Eng & Tech. Gautam Buddha Nagar, India
| |
Collapse
|
|
2
|
Naeem A, Hu P, Yang M, Zhang J, Liu Y, Zhu W, Zheng Q. Natural Products as Anticancer Agents: Current Status and Future Perspectives. Molecules 2022; 27:molecules27238367. [PMID: 36500466 PMCID: PMC9737905 DOI: 10.3390/molecules27238367] [Citation(s) in RCA: 189] [Impact Index Per Article: 63.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2022] [Revised: 11/22/2022] [Accepted: 11/28/2022] [Indexed: 12/02/2022] Open
Abstract
Natural products have been an invaluable and useful source of anticancer agents over the years. Several compounds have been synthesized from natural products by modifying their structures or by using naturally occurring compounds as building blocks in the synthesis of these compounds for various purposes in different fields, such as biology, medicine, and engineering. Multiple modern and costly treatments have been applied to combat cancer and limit its lethality, but the results are not significantly refreshing. Natural products, which are a significant source of new therapeutic drugs, are currently being investigated as potential cytotoxic agents and have shown a positive trend in preclinical research and have prompted numerous innovative strategies in order to combat cancer and expedite the clinical research. Natural products are becoming increasingly important for drug discovery due to their high molecular diversity and novel biofunctionality. Furthermore, natural products can provide superior efficacy and safety due to their unique molecular properties. The objective of the current review is to provide an overview of the emergence of natural products for the treatment and prevention of cancer, such as chemosensitizers, immunotherapeutics, combinatorial therapies with other anticancer drugs, novel formulations of natural products, and the molecular mechanisms underlying their anticancer properties.
Collapse
Affiliation(s)
- Abid Naeem
- Key Laboratory of Modern Preparation of Chinese Medicine, Ministry of Education, Jiangxi University of Chinese Medicine, Nanchang 330004, China
| | - Pengyi Hu
- Key Laboratory of Modern Preparation of Chinese Medicine, Ministry of Education, Jiangxi University of Chinese Medicine, Nanchang 330004, China
| | - Ming Yang
- Key Laboratory of Modern Preparation of Chinese Medicine, Ministry of Education, Jiangxi University of Chinese Medicine, Nanchang 330004, China
| | - Jing Zhang
- Key Laboratory of Modern Preparation of Chinese Medicine, Ministry of Education, Jiangxi University of Chinese Medicine, Nanchang 330004, China
| | - Yali Liu
- Key Laboratory of Pharmacodynamics and Safety Evaluation, Health Commission of Jiangxi Province, Nanchang Medical College, Nanchang 330006, China
- Key Laboratory of Pharmacodynamics and Quality Evaluation on Anti-Inflammatory Chinese Herbs, Jiangxi Administration of Traditional Chinese Medicine, Nanchang Medical College, Nanchang 330006, China
| | - Weifeng Zhu
- Key Laboratory of Modern Preparation of Chinese Medicine, Ministry of Education, Jiangxi University of Chinese Medicine, Nanchang 330004, China
| | - Qin Zheng
- Key Laboratory of Modern Preparation of Chinese Medicine, Ministry of Education, Jiangxi University of Chinese Medicine, Nanchang 330004, China
- Correspondence:
| |
Collapse
|
|
3
|
Sayed AM, Gohar OM, Abd-Alhameed EK, Hassanein EHM, Ali FEM. The importance of natural chalcones in ischemic organ damage: Comprehensive and bioinformatic analysis review. J Food Biochem 2022; 46:e14320. [PMID: 35857486 DOI: 10.1111/jfbc.14320] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2022] [Revised: 07/01/2022] [Accepted: 07/07/2022] [Indexed: 11/26/2022]
Abstract
Over the last few decades, extensive research has been conducted, yielding a detailed account of thousands of newly discovered compounds of natural origin and their biological activities, all of which have the potential to be used for a wide range of therapeutic purposes. There are multiple research papers denoting the central objective of chalcones, which have been shown to have therapeutic potential against various forms of ischemia. The various aspects of chalcones are discussed in this review regarding molecular mechanisms involved in the promising anti-ischemic potential of these chalcones. The main mechanisms involved in these protective effects are Nrf2/Akt activation and NF-κB/TLR4 suppression. Furthermore, in-silico studies were carried out to discover the probable binding of these chalcones to Keap-1 (an inhibitor of Nrf2), Akt, NF-κB, and TLR4 protein molecules. Besides, network pharmacology analysis was conducted to predict the interacting partners of these signals. The obtained results indicated that Nrf2, Akt, NF-κB, and TLR4 are involved in the beneficial anti-ischemic actions of chalcones. Conclusively, the present findings show that chalcones as anti-ischemic agents have a valid rationale. The discussed studies will provide a comprehensive viewpoint on chalcones and can help to optimize their effects in different ischemia. PRACTICAL APPLICATIONS: Ischemic organ damage is an unavoidable pathological condition with a high worldwide incidence. According to the current research progress, natural chalcones have been proved to treat and/or prevent various types of ischemic organ damage by alleviating oxidative stress, inflammation, and apoptosis by different molecular mechanisms. This article displays the comprehensive research progress and the molecular basis of ischemic organ damage pathophysiology and introduces natural chalcones' mechanism in the ischemic organ condition.
Collapse
Affiliation(s)
- Ahmed M Sayed
- Biochemistry Laboratory, Chemistry Department, Faculty of Science, Assiut University, Assiut, Egypt
| | - Osama M Gohar
- Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Assiut, Egypt
| | - Esraa K Abd-Alhameed
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt
| | - Emad H M Hassanein
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Assiut, Egypt
| | - Fares E M Ali
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Assiut, Egypt
| |
Collapse
|
|
4
|
Hu C, Li L. The immunoregulation of mesenchymal stem cells plays a critical role in improving the prognosis of liver transplantation. J Transl Med 2019; 17:412. [PMID: 31823784 PMCID: PMC6905033 DOI: 10.1186/s12967-019-02167-0] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2019] [Accepted: 12/04/2019] [Indexed: 12/14/2022] Open
Abstract
The liver is supplied by a dual blood supply, including the portal venous system and the hepatic arterial system; thus, the liver organ is exposed to multiple gut microbial products, metabolic products, and toxins; is sensitive to extraneous pathogens; and can develop liver failure, liver cirrhosis and hepatocellular carcinoma (HCC) after short-term or long-term injury. Although liver transplantation (LT) serves as the only effective treatment for patients with end-stage liver diseases, it is not very popular because of the complications and low survival rates. Although the liver is generally termed an immune and tolerogenic organ with adaptive systems consisting of humoral immunity and cell-mediated immunity, a high rejection rate is still the main complication in patients with LT. Growing evidence has shown that mesenchymal stromal cell (MSC) transplantation could serve as an effective immunomodulatory strategy to induce tolerance in various immune-related disorders. MSCs are reported to inhibit the immune response from innate immune cells, including macrophages, dendritic cells (DCs), natural killer cells (NK cells), and natural killer T (NKT) cells, and that from adaptive immune cells, including T cells, B cells and other liver-specific immune cells, for the generation of a tolerogenic microenvironment. In this review, we summarized the relationship between LT and immunoregulation, and we focused on how to improve the effects of MSC transplantation to improve the prognosis of LT. Only after exhaustive clarification of the potential immunoregulatory mechanisms of MSCs in vitro and in vivo can we implement MSC protocols in routine clinical practice to improve LT outcome.
Collapse
Affiliation(s)
- Chenxia Hu
- Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China.,National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China
| | - Lanjuan Li
- Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China. .,National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China.
| |
Collapse
|
|
5
|
Lu H, Dai X, Li X, Sun Y, Gao Y, Zhang C. Gal-1 regulates dendritic cells-induced Treg/Th17 balance though NF-κB/RelB-IL-27 pathway. ANNALS OF TRANSLATIONAL MEDICINE 2019; 7:628. [PMID: 31930029 DOI: 10.21037/atm.2019.11.02] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
Background This study aimed to investigate the mechanism of galectin (Gal)-1 of regulating Treg/Th17 in pathogenesis of acute rejection after liver transplantation in rat. Methods Mononuclear cells were induced to immature dendritic cells (imDCs), which were transfected with or without NF-κB/RelB. Western Blot was performed to detect the expression of NF-κB/RelB. the expression of CD11c, CD45RB, CD80 and MHC II were detected by flow cytometry. Enzyme-linked immunosorbent assay (ELISA) was employed to detect cytokines IL-27 and TGF-β. Lewis and dark agouti (DA) rats were generally anaesthetized by isoflurane inhalation to establish liver transplant models. Results We demonstrate that Gal-1 disturbs maturation of imDCs by downregulating NF-κB/RelB expression, and Gal-1 negatively controls CD4+ proliferation though IL-27 pathway. Conclusions In aggregate, Gal-1 promotes Treg differentiation in CD4+ T cells though NF-κB/RelB-IL-27 pathway. These findings suggest a new therapeutic target to mediate Treg population.
Collapse
Affiliation(s)
- Hao Lu
- Department of Liver Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210000, China
| | - Xinzheng Dai
- Department of Liver Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210000, China
| | - Xu Li
- Department of Liver Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210000, China
| | - Yu Sun
- Department of Liver Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210000, China
| | - Yangjuan Gao
- Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210000, China
| | - Chuanyong Zhang
- Department of Liver Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210000, China
| |
Collapse
|
|
6
|
Huang H, Lu Y, Zhou T, Gu G, Xia Q. Innate Immune Cells in Immune Tolerance After Liver Transplantation. Front Immunol 2018; 9:2401. [PMID: 30473690 PMCID: PMC6237933 DOI: 10.3389/fimmu.2018.02401] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2018] [Accepted: 09/27/2018] [Indexed: 12/13/2022] Open
Abstract
Currently, liver transplantation is the most effective treatment for end-stage liver disease. Immunosuppressive agents are required to be taken after the operations, which have significantly reduced rejection rates and improved the short-term (<1 year) survival rates. However, post-transplant complications related to the immunosuppressive therapy have led to the development of new protocols aimed at protecting renal function and preventing de novo cancer and dysmetabolic syndrome. Donor specific immune tolerance, which means the mature immune systems of recipients will not attack the grafts under the conditions without any immunosuppression therapies, is considered the optimal state after liver transplantation. There have been studies that have shown that some patients can reach this immune tolerance state after liver transplantation. The intrahepatic immune system is quite different from that in other solid organs, especially the innate immune system. It contains a variety of liver specific cells, such as liver-derived dendritic cells, Kupffer cells, liver sinusoidal endothelial cells, liver-derived natural killer (NK) cells, natural killer T (NKT) cells, and so on. Depending on their specific structures and functions, these intrahepatic innate immune cells play important roles in the development of intrahepatic immune tolerance. In this article, in order to have a deeper understanding of the tolerogenic functions of liver, we summarized the molecular mechanisms of immune tolerance induced by intrahepatic innate immune cells after liver transplantation.
Collapse
Affiliation(s)
- Hongting Huang
- Department of Hepatic Surgery and Liver Transplantation Center, School of Medicine, Renji Hospital, Shanghai Jiaotong University, Shanghai, China
| | - Yefeng Lu
- Department of Hepatic Surgery and Liver Transplantation Center, School of Medicine, Renji Hospital, Shanghai Jiaotong University, Shanghai, China
| | - Tao Zhou
- Department of Hepatic Surgery and Liver Transplantation Center, School of Medicine, Renji Hospital, Shanghai Jiaotong University, Shanghai, China
| | - Guangxiang Gu
- Department of Hepatic Surgery and Liver Transplantation Center, School of Medicine, Renji Hospital, Shanghai Jiaotong University, Shanghai, China
| | - Qiang Xia
- Department of Hepatic Surgery and Liver Transplantation Center, School of Medicine, Renji Hospital, Shanghai Jiaotong University, Shanghai, China
| |
Collapse
|
|
7
|
Fahrner R, Dondorf F, Ardelt M, Settmacher U, Rauchfuss F. Role of NK, NKT cells and macrophages in liver transplantation. World J Gastroenterol 2016; 22:6135-6144. [PMID: 27468206 PMCID: PMC4945975 DOI: 10.3748/wjg.v22.i27.6135] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2016] [Revised: 05/25/2016] [Accepted: 06/15/2016] [Indexed: 02/07/2023] Open
Abstract
Liver transplantation has become the treatment of choice for acute or chronic liver disease. Because the liver acts as an innate immunity-dominant organ, there are immunological differences between the liver and other organs. The specific features of hepatic natural killer (NK), NKT and Kupffer cells and their role in the mechanism of liver transplant rejection, tolerance and hepatic ischemia-reperfusion injury are discussed in this review.
Collapse
|
|
8
|
Zhang AY, Liu YM, Gong JP. Kupffer cells and liver transplantation. Shijie Huaren Xiaohua Zazhi 2015; 23:1917-1923. [DOI: 10.11569/wcjd.v23.i12.1917] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Nowadays, liver transplantation is globally considered the most effective treatment for end-stage liver diseases. Ischemia-reperfusion (I/R) injury and immune rejection response (IRR) are the two major imperfections which severely affect the recipients' prognosis and survival rate without satisfactory clinical management strategies. Therefore, exploring effective methods to improve I/R injury and IRR have important clinical significance under circumstances of shortage of donor livers. Kupffer cells (KCs) are the largest population of antigen representing cells (APCs) which settle in the liver. As the first defensive line of the live, KCs exhibit various biological effects. However, the exact mechanisms responsible for the role of KCs in I/R injury and IRR remain elusive. We hereby review the current finding about the role of KCs in I/R injury and IRR.
Collapse
|
|
9
|
Kupffer Cells in Health and Disease. MACROPHAGES: BIOLOGY AND ROLE IN THE PATHOLOGY OF DISEASES 2014. [PMCID: PMC7121975 DOI: 10.1007/978-1-4939-1311-4_10] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
Kupffer cells (KC), the resident macrophages of the liver, represent the largest population of mononuclear phagocytes in the body. Phenotypic, developmental, and functional aspects of these cells in steady state and in different diseases are the focus of this review. Recently it has become evident that KC precursors seed the liver already early in fetal development, and the population can be maintained independently from circulating monocytes. However, inflammatory conditions allow rapid differentiation of monocytes into mature cells that are indistinguishable from genuine KC. KC are located in the lumen of sinusoids that receive blood both from the portal vein, carrying nutrients and microbial products from the gut, and from the hepatic artery. This positions KC ideally for their prime function, namely surveillance and clearance of the circulation. As such, they are important in iron recycling by phagocytosing effete erythrocytes, for instance. The immunophenotype of KC, characterized by a wide variety of endocytic receptors, is indicative of this scavenger function. In maintaining homeostasis, KC have an ambivalent response to exogenous triggers. On the one hand, their surveillance function requires alert responses to potentially hazardous substances. On the other hand, continuous exposure of the cells to the trigger-rich content of blood originating from the gut dampens their responsiveness to further stimuli. This ambivalence is also reflected in their diverse roles in disease pathogenesis. For the latter, we sketch the contribution of KC by giving examples of their role in metabolic disease, infections, and liver injury.
Collapse
|